Fig. 5: Iron-rich scar regions undergoing lipomatous metaplasia exhibit perpetual macrophage ingress, M1 macrophage polarization, foam cell formation, and expansion of the “death zone” in the early phase of chronic hemorrhagic MI. | Nature Communications

Fig. 5: Iron-rich scar regions undergoing lipomatous metaplasia exhibit perpetual macrophage ingress, M1 macrophage polarization, foam cell formation, and expansion of the “death zone” in the early phase of chronic hemorrhagic MI.

From: Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium

Fig. 5: Iron-rich scar regions undergoing lipomatous metaplasia exhibit perpetual macrophage ingress, M1 macrophage polarization, foam cell formation, and expansion of the “death zone” in the early phase of chronic hemorrhagic MI.The alternative text for this image may have been generated using AI.

Representative serial paraffin histology sections from 8-week-old hemorrhagic MI were stained with Panel a: elastin-modified Masson’s trichrome (EMT) stain, H&E, Prussian Blue (PB), as well as Panel b: anti-Cleaved Caspase 3 (CC3), anti-MAC387, anti-E06, anti-IL-1β, anti-TNF-α, anti-MMP-9, anti-CD163, anti-CD36, and anti-GLUT-1 antibodies. Autofluorescence of ceroid was examined in sections stained with PB stain and E06 antibody (PB-1 and E06-1). Excitation wavelength: 405 nm and emission wavelength: 428–496 nm (PB-2 and E06-2). Differential interference contrast (DIC) (PB-3 and E06-3) overlay. Note the extensive co-localization of ceroid with iron deposits (PB, blue staining) and foam cells. Positive immunohistochemical (IHC) staining with anti-CC3 antibody confirmed the ongoing apoptosis of iron-laden macrophage-derived foam cells (red stain; arrows). Positive IHC staining with MAC387 antibody (brown staining) indicates that new macrophages are continually recruited to the regions with apoptotic iron-laden macrophage-derived ceroid-rich foam cells. Note also the extensive co-localization of ceroid with E06-stained oxidized phospholipids (E06, brown staining) in foam cell-rich regions. Positive staining for pro-inflammatory macrophage markers (IL-1β, TNF-α, and MMP-9; all stained red) indicates that iron-laden macrophage-derived in the ceroid-rich regions preferentially polarize to pro-inflammatory M1 phenotype. CD163-positive staining (pink stain) in iron-rich regions undergoing LM indicates perpetual iron-induced macrophage induction and iron-laden macrophage-to-foam cell transformation. Staining with CD36 antibody confirmed the presence of foam cells. Glycolytic M1 macrophage phenotype in macrophages undergoing foam cell transformation was also demonstrated by intense immunoreactivity for GLUT-1. Scale bar equals 50 µm. Additional zoomed-in regions can be found in Supplementary Fig. 3. The number of samples per timepoint/animal group used is depicted in Supplementary Fig. 1.

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